Abstract
Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8(+) T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8(+), IFN-γ-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.
Trial registration:
ClinicalTrials.gov NCT01001650.
Publication types
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Clinical Trial
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adolescent
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Adult
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Animals
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Antibodies, Protozoan / blood
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Antibodies, Protozoan / immunology
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Antigens, Protozoan / immunology
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CD8-Positive T-Lymphocytes / immunology*
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Humans
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Injections, Intravenous
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Injections, Subcutaneous
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Interferon-gamma / biosynthesis
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Interferon-gamma / immunology
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Liver / immunology*
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Macaca mulatta
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Malaria Vaccines / administration & dosage
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Malaria Vaccines / adverse effects
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Malaria Vaccines / immunology*
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Malaria, Falciparum / prevention & control*
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Mice
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Middle Aged
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Plasmodium falciparum / immunology*
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Rabbits
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Sporozoites / immunology*
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Vaccines, Attenuated / administration & dosage
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Vaccines, Attenuated / adverse effects
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Vaccines, Attenuated / immunology
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Young Adult
Substances
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Antibodies, Protozoan
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Antigens, Protozoan
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Malaria Vaccines
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Vaccines, Attenuated
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Interferon-gamma
Associated data
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ClinicalTrials.gov/NCT01001650